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2011 Grants - D'Amelio

Preventing and Monitoring Onset of Synaptic Degeneration in Early Alzheimer's Disease

Marcello D'Amelio, Ph.D.
IRCCS Santa Lucia Foundation
Rome, Italy

2011 New Investigator Research Grant

The early stages of Alzheimer's disease are characterized by damage to synapses, the tiny cellular regions through which brain cells send and receive chemical messages. Synaptic damage can lead to cognitive decline. However, scientists do not understand exactly how Alzheimer's-related synaptic loss occurs in the brain.

Marcello D'Amelio, Ph.D., and colleagues have been studying how synaptic damage may occur in mice engineered to produce Alzheimer's-like pathology. Preliminary results have shown that a protein called caspase-3 becomes abnormally activated in mouse brains and causes damage to branchlike extensions of the animals' neurons. These extensions are where synapses often exist. Such abnormal activity is caused by improper functioning of mitochondria — the cellular structures that produce energy for brain cells. In addition, the team has observed that another memory-related molecule called phosphatidylserine may also be abnormally activated in synaptic regions.

For this grant, Dr. D'Amelio and colleagues will expand on their earlier studies. They will treat Alzheimer's-like mice with drugs that target abnormal mitochondrial function. They will then use imaging procedures to assess whether their treatment prevented caspase-3-related synaptic damage and memory loss in the mice. The team will also use imaging techniques to assess the relationship between phosphatidylserine levels and early synaptic loss in the animals' brains. Such efforts could shed new light on the biological mechanisms underlying early-stage Alzheimer's disease, and they could lead to better ways of diagnosing the disease and developing drug therapies.